Hypothyroidism is one of the most common canine endocrine disorders. To determine hypothyroidism, many practicing veterinarians use several different tests to arrive at a diagnosis. These tests include thyroxine (T4), triiodothyronine (T3), thyroglobulin autoantibody (TgAA), canine thyrotropin (cTSH), free thyroxine (Free T4), Free thyroxine by dialysis (Free T4D), reverse triiodothyronine (rT3), and reverse thyroxine (rT4). Most labs do not provide all of these tests. Therefore, the veterinarian must use whatever test results the lab provides to determine the thyroid status of the animal. In the past, TSH has been obtained from bovine pituitaries and used to stimulate the thyroid gland to produce T4. Based on this T4 stimulation test, the veterinarian can determine whether an animal has primary hypothyroidism.
Although the T4 stimulation tests remains, in principle, a viable way to diagnose hypothyroidism, bovine TSH is no longer considered an acceptable test component. Because of the pituitary's location, bovine pituitary derivatives pose a particular danger for transmission of bovine spongioform encephalitis (“BSE”, commonly known as “mad cow disease”). Bovine products may also transmit rabies and other diseases. They also suffer from cost ($70-$80 per dose) and availability problems. Even when bovine TSH is available, the purity and potency varies greatly from lot to lot, making reliable testing difficult. Further, bovine TSH has not been approved for use in the canine. While human recombinant TSH may be used in the place of canine TSH in this and other applications, it is expensive (at least $130 per dose). Both bovine and human TSH may invoke an immune response after the first administration, interfering with repeated testing or treatment.
To overcome the problems associated with bovine TSH, various systems have been developed to produce recombinant TSH, including an E. coli system and a conventional baculovirus-insect cell system. However, neither system can produce sialylated recombinant TSH, which is necessary for an efficacious in vivo test in any mammal. The un-sialylated TSH may not be used as a direct substitute for bovine TSH in previous methods designed for bovine TSH methods. In fact, the un-sialylated insect-specific glycans on TSH produced with the previous baculovirus-insect system would signal its rapid clearance from the canine circulatory system. Although sialylated TSH is currently produced in mammalian cells, these cells tend to produce protein only at low levels and are expensive to cultivate.